The supplemental biologics license application (sBLA) submitted by Genentech (Roche), atezolizumab’s manufacturer, is based on the phase III IMpower133 study, in which the addition of atezolizumab to standard upfront carboplatin and etoposide significantly prolonged survival in patients with ES-SCLC.
The FDA action date for a decision on the sBLA is March 18, 2019.
After a median follow-up of 13.9 months, the median overall survival (OS) in IMpower133 was 12.3 months (95% CI, 10.8-15.9) in the atezolizumab arm compared with 10.3 months (95% CI, 9.3-11.3) in the placebo arm (HR, 0.70; 95% CI, 0.54-0.91; P= .0069)—a 30% reduction in the risk of death. OS events occurred in 51.7% of the atezolizumab arm and 66.3% of the control arm.
Median progression-free survival (PFS) was 5.2 months (95% CI, 4.4-5.6) in the atezolizumab group compared with 4.3 months (95% CI, 4.2-4.5) in the placebo group (HR, 0.77; 95% CI, 0.62-0.96; P = .017). Atezolizumab was associated with a higher 6-month PFS rate (30.9% vs. 22.4%), and a more than doubling 12-month PFS rate (12.6% vs 5.4%) compared with placebo.
“It’s been more than 20 years since there has been a new initial treatment option for extensive-stage small cell lung cancer that delivers a clinically meaningful survival benefit,” Sandra Horning, MD, chief medical officer and head of Global Product Development, Genentech (Roche), said in a statement.
“We are working closely with the FDA to bring this Tecentriq-based regimen to people with this difficult-to-treat type of lung cancer as soon as possible,” added Horning.
The global, double-blind, randomized, placebo-controlled phase I/III IMpower133 trial evaluated the efficacy and safety of first-line atezolizumab as adjunctive therapy to standard of care, combination carboplatin and etoposide, in 403 treatment-naïve patients with ES-SCLC.
Results from the study were presented at the 19th World Conference on Lung Cancer.1 The results were simultaneously published in the New England Journal of Medicine.2
All patients received four 21-day cycles of carboplatin AUC 5 mg/mL/min IV on day 1 and 100 mg/m2 etoposide IV on days 1 through 3. Patients were also randomized 1:1 to receive either concurrent atezolizumab at 1200 mg IV on day 1 (n = 201) or placebo (n = 202) during the induction phase. Treatment was followed by maintenance therapy with atezolizumab or placebo, according to the previous random assignment, every 3 weeks until progressive disease or loss of clinical benefit.
Investigator-assessed PFS and OS in the intention-to-treat population served as the primary endpoints. Secondary endpoints included objective response rate (ORR), duration of response, and safety.
Age, demographics, and smoking status were representative of the disease: median age was 64 years (range, 26-90) in both the atezolizumab and placebo groups, and the majority were male (64% vs 65%, respectively), white (81% vs 79%), and former smokers (58.7% vs 61.4%). The atezolizumab arm included 17 patients (8%) with brain metastases and 77 (38%) with liver metastases; while the placebo group consisted of 9% and 36%, respectively.
The median duration of treatment with atezolizumab was 4.7 months, with a median of 7 doses received. The investigators saw no major difference in ORR between arms (60.2% vs 64.4%, respectively) or in median duration of response (4.2 vs 3.9 months).
Atezolizumab demonstrated superior 6-month (32.2% vs 17.1%) and 12-month (14.9% vs 6.2%) event-free rates. Eighteen patients treated with concurrent atezolizumab had ongoing responses compared with only 7 patients in the control arm.
The safety profile of the regimen appeared consistent with the previously reported safety profile of the individual agents, with no new findings observed.
The most common grade 1/2 treatment-related AEs among the atezolizumab and placebo arms included neutropenia (13.1% vs 10.2%, respectively), anemia (24.7% vs 20.9%), decreased neutrophil count (3.5% vs 6.1%), thrombocytopenia (6.1% vs 7.1%), and leukopenia (7.6% vs 5.1%).
Immune-related adverse events (IRAEs) were more common with atezolizumab compared with placebo (39.9% vs 24.5%). The most common grade 1 or 2 IRAEs among the atezolizumab and placebo arms included rash (16.7% vs 10.2%, respectively), hepatitis (5.6% vs 4.6%), infusion-related reactions (3.5% vs 4.6%), pneumonitis (1.5% vs 1.5%), and colitis (0.5% vs 0%).
Atezolizumab has approved FDA indications for non–small cell lung cancer and urothelial carcinoma.
- Liu S, Mansfield A, Szczesna S, et al. IMpower 133: Primary PFS, OS and Safety in a PH1/3 Study of 1L Atezolizumab + Carboplatin + Etoposide in Extensive-Stage SCLC. Presented at: the IASLC 19th World Conference on Lung Cancer; September 23-26; Toronto, Canada. Abstract PL02.07.
- Liu S, Mansfield A, Szczesna S, et al. First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer. NEJM. 2018;doi:10.1056/NEJMoa1809064.
This article was originally published by OncLive® as “FDA Grants Atezolizumab Regimen Priority Review for Frontline SCLC.”